Oligodendrocyte Lineage Cell Mechanisms of Axon Selection for Myelination

项目摘要 少突胶质细胞是中枢神经系统的常驻髓鞘形成细胞类型。最近的研究表明 不同种类的神经元沿着轴突有不同的髓鞘沿着分布。但只有 最近，人们从髓鞘形成的角度考虑了轴突的身份。因此， 轴突信号传导和髓鞘形成的选择在很大程度上仍然是未知的。我们的实验室和其他实验室已经证明， 神经元活动增加髓鞘形成，突触囊泡释放沿着髓鞘下的轴突发生 鞘，表明少突胶质细胞可能需要能够接收和解释神经递质信号。 单个少突胶质细胞可以形成多达40个不同的轴突，这是一种独特的情况， 细胞可能需要适应来自许多不同神经元的信号。如何实现这一点？少突 表达许多典型的突触后因子，表面上有助于轴突和髓鞘之间的信号传导， 但是这些蛋白质在髓鞘形成细胞中的作用还很不清楚。使用斑马鱼模型，该提案 将利用遗传方法和体内成像来解决两个基本概念： 这些突触后因子在少突胶质细胞中的表达和/或定位， 以及它们在髓鞘形成过程中的作用。完成这项工作的方法是 有两个目标：目标1测试什么样的突触后因子被表达，这些突触后蛋白定位在哪里， 以及它们在什么时候是重要的; Aim 2测试了这些蛋白质如何促进髓鞘形成，以及如果有 是轴突身份与髓鞘形成中突触后蛋白的定位和功能之间的相关性 少突胶质细胞

PROJECT SUMMARY Oligodendrocytes are the resident myelinating cell type of the central nervous system. Recent work indicates that different classes of neurons have differing patterns and distribution of myelin along their axons. Yet only recently has the identity of the axons been considered with respect to myelination. Thus, the mechanisms of axon signaling and selection for myelination remain largely unknown. Our lab and others have shown that neuronal activity increases myelination and synaptic vesicle release occurs along axons underneath myelin sheaths, suggesting oligodendrocytes may need to be able to receive and interpret neurotransmitter signaling. A single oligodendrocyte can myelinate up to 40 distinct axons, posing a unique situation where an individual cell may need to adapt to signaling from many different neurons. How might this be achieved? Oligodendrocytes express many canonical post-synaptic factors, ostensibly to aid in signaling between the axon and myelin sheath, but the role these proteins play in myelinating cells is largely unknown. Using a zebrafish model, this proposal will utilize genetic approaches and in vivo imaging to address two fundamental concepts: is there a pattern to the expression and/or localization of these post-synaptic factors in oligodendrocytes and does this correspond to wrapped axonal identity; and what function do they serve in the process of myelination. This will be achieved in two aims: Aim 1 tests what post-synaptic factors are expressed, where these post-synaptic proteins localize, and when are they important; and Aim 2 tests how these proteins function to facilitate myelination, and if there is a correlation between axon identity and localization and function of post-synaptic proteins in myelinating oligodendrocytes.